Cloning, mapping, and retinal expression of the canine ciliary neurotrophic factor receptor a (CNTFRα)

被引:41
作者
Beltran, WA
Zhang, Q
Kijas, JW
Gu, DN
Rohrer, H
Jordan, JA
Aguirre, GD [1 ]
机构
[1] Cornell Univ, New York State Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA
[2] Max Planck Inst Hirnforsch, D-60528 Frankfurt, Germany
关键词
D O I
10.1167/iovs.02-0763
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. To clone, map, and determine the site of expression (mRNA and protein) of the a subunit of the receptor for ciliary neurotrophic factor (CNTFRalpha) in the normal adult canine retina. METHODS. The complete coding sequence of the canine CNTFRa cDNA was cloned, and radiation hybrid (RH) mapping was used to determine the chromosomal localization of the gene. CNTFRa mRNA expression in retina and other tissues was examined by reverse transcription-polynterase chain reaction. The cellular distribution of CNTFRa in the canine retina was studied by in situ hybridization and immunocytochemistry. RESULTS. Canine CNTFRa shares a high degree of homology with the human, mouse, and rat coding sequences, both at the nucleotide and amino acid level, but has lower homology with the chicken. CNTFRa was RH mapped to CFA 11 (Canis familiaris autosome 11) in the dog, a region showing homology to the short arm of human chromosome 9 (9P13). The gene is transcribed in retina, brain, spleen, lung, liver, and kidney. In the retina, CNTFRa was highly expressed by photoreceptors, but both the transcript and protein were also found in the RPE, inner nuclear layer, and ganglion cells. CONCLUSIONS. These findings demonstrate that CNTFRa is expressed by rods and cones in the normal adult canine retina and suggest that ciliary neurotrophic factor (CNTF) could have a direct photoreceptor rescue effect by binding to CNTFRa in these cells. This could open novel pathways for the treatment of retinal degeneration in animal models and humans.
引用
收藏
页码:3642 / 3649
页数:8
相关论文
共 30 条
[2]  
BOULTON TG, 1994, J BIOL CHEM, V269, P11648
[3]   Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid/linkage map of the domestic dog genome to all chromosomes [J].
Breen, M ;
Jouquand, S ;
Renier, C ;
Mellersh, CS ;
Hitte, C ;
Holmes, NG ;
Chéron, A ;
Suter, N ;
Vignaux, F ;
Bristow, AE ;
Priat, C ;
McCann, E ;
André, C ;
Boundy, S ;
Gitsham, P ;
Thomas, R ;
Bridge, WL ;
Spriggs, HF ;
Ryder, EJ ;
Curson, A ;
Sampson, J ;
Ostrander, EA ;
Binns, MM ;
Galibert, F .
GENOME RESEARCH, 2001, 11 (10) :1784-1795
[4]   Adenovirus-mediated gene transfer of ciliary neurotrophic factor can prevent photoreceptor degeneration in the retinal degeneration (rd) mouse [J].
Cayouette, M ;
Gravel, C .
HUMAN GENE THERAPY, 1997, 8 (04) :423-430
[5]  
Cayouette M, 1998, J NEUROSCI, V18, P9282
[6]  
Chong NHV, 1999, INVEST OPHTH VIS SCI, V40, P1298
[7]   LIFR-BETA AND GP-130 AS HETERODIMERIZING SIGNAL TRANSDUCERS OF THE TRIPARTITE CNTF RECEPTOR [J].
DAVIS, S ;
ALDRICH, TH ;
STAHL, N ;
PAN, L ;
TAGA, T ;
KISHIMOTO, T ;
IP, NY ;
YANCOPOULOS, GD .
SCIENCE, 1993, 260 (5115) :1805-1808
[8]   RELEASED FORM OF CNTF RECEPTOR-ALPHA COMPONENT AS A SOLUBLE MEDIATOR OF CNTF RESPONSES [J].
DAVIS, S ;
ALDRICH, TH ;
IP, NY ;
STAHL, N ;
SCHERER, S ;
FARRUGGELLA, T ;
DISTEFANO, PS ;
CURTIS, R ;
PANAYOTATOS, N ;
GASCAN, H ;
CHEVALIER, S ;
YANCOPOULOS, GD .
SCIENCE, 1993, 259 (5102) :1736-1739
[9]   THE RECEPTOR FOR CILIARY NEUROTROPHIC FACTOR [J].
DAVIS, S ;
ALDRICH, TH ;
VALENZUELA, DM ;
WONG, V ;
FURTH, ME ;
SQUINTO, SP ;
YANCOPOULOS, GD .
SCIENCE, 1991, 253 (5015) :59-63
[10]   LOCALIZATION OF THE GENE FOR THE CILIARY NEUROTROPHIC FACTOR-RECEPTOR (CNTFR) TO HUMAN CHROMOSOME-9 [J].
DONALDSON, DH ;
BRITT, DE ;
JONES, C ;
JACKSON, CL ;
PATTERSON, D .
GENOMICS, 1993, 17 (03) :782-784